Decanolides, isolated from various fungal metabolites have attracted considerable attention due to the interesting biological properties and scare availability of macrolides. Aspinolide A, its diastereomer Stagonoide F, Stagonolide C, Stagonolide E and several other decanolides have been isolated from cultures of various fungii. Few syntheses of these important Macrolides are known most of which involves the use of kinetic resolution for generating chirality or based on chiral pool approach involving large number of steps.
T. Mahapatra et al. in Bull. Chem. Soc. Jpn., 2011, 84 (5), 511-519 describes efficient asymmetric synthesis of naturally occurring small ring macrolide, stagonolide-D and stagonolide-G from (S)-ethyl lactate as a chiral pool. Further a convergent and efficient total synthesis of stagonolide C exploits the high configuration control in the Prins cyclization along with alkene rearrangement and ring-closing metathesis as key steps is reported. in Helvetica Chimica Acta. 95 (2) 227-324 February 2012 by Jhillu S. Yadav et al. The nonenolides such as Stagonolides G to Stagonolides I and Modiolide A are disclosed in J. Nat. Prod., 2008, 71 (11), 1897-1901. The stereoselective total synthesis of Stagonolide G is disclosed in Tetrahedron Letters, 51 (21) 2010, 2903-2905.
The stereoselective total synthesis of the nonenolide, (+)-stagonolide B involves epoxide homologation, hydrolytic kinetic resolution and ring-closing metathesis is described in Synthesis 2010(6): 1039-1045.
Tetrahedron Letters 53, (2) January 2012, 256-258 discloses chemoenzymatic asymmetric total synthesis of small ring macrolide stagonolide-E comprises ruthenium(II), enzyme combo dynamic kinetic resolution reaction, whereas Synlett 2009 (18) 2924-2926 describes stereoselective total synthesis of (−)-(6R,11R,14R)-Colletallol comprises Jacobsen's hydrolytic kinetic resolution (HKR) and ring-closing metathesis protocol.
Further the synthesis of 9-membered macrolide, stagonolide-F (3), wherein Jacobsen's hydrolytic kinetic resolution (HKR) and Sharpless epoxidation is used for the creation of two stereogenic centers is reported in Bioorganic Chemistry 37 (2), 2009, 46-51.
Tetrahedron Letters 53, (9), February 2012, 1153-1155 discloses total synthesis of stagonolide C using chiral pool strategy. Novel synthesis of putaminoxin, stagonolide-F and aspinolide-A have been achieved by utilizing (S) and (R)-malic acid is known from Letters in Organic Chemistry, 8, (2), February 2011, 143-149 (7).
In view of foregoing most of the process in the prior art involves chiral pool strategy, use of expensive and toxic metal catalyst, also gives poor yield and entioselectivity of desired decanolides or nonenolides. Further, the lengthy steps in the prior art impact the overall yield of the decanolides.
The present inventors therefore felt a need to develop enantioselective synthesis of biologically active natural product based on asymmetric organocatalysis by a simple, concise and flexible route with reduced number of process steps using non chiral, cheaper, easily available starting material.